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  • Conference paper
    Saleh A, Meng C, Chan M, Alton EWFW, Griesenbach Uet al., 2018,

    RNA in-situ hybridisation is able to quantify lentiviral transduction of respiratory epithelium

    , Annual Conference of the British-Society-for-Gene-and-Cell-Therapy, Publisher: MARY ANN LIEBERT, INC, Pages: A7-A7, ISSN: 1043-0342
  • Journal article
    Turnbull AR, Murphy R, Behrends V, Lund-Palau H, Simbo A, Mariveles M, Alton EW, Bush A, Shoemark A, Davies JCet al., 2018,

    Impact of T2R38 receptor polymorphisms on pseudomonas aeruginosa infection in cystic fibrosis

    , American Journal of Respiratory and Critical Care Medicine, Vol: 197, Pages: 1635-1638, ISSN: 1073-449X
  • Journal article
    Dunning J, Blankley S, Hoang LT, Cox M, Graham CM, James PL, Bloom CI, Chaussabel D, Banchereau J, Brett SJ, Moffatt MF, OGarra A, Openshaw PJMet al., 2018,

    Progression of whole-blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in severe influenza

    , Nature Immunology, Vol: 19, Pages: 625-635, ISSN: 1529-2916

    Transcriptional profiles and host-response biomarkers are used increasingly to investigate the severity, subtype and pathogenesis of disease. We now describe whole-blood mRNA signatures and concentrations of local and systemic immunological mediators in 131 adults hospitalized with influenza, from whom extensive clinical and investigational data were obtained by MOSAIC investigators. Signatures reflective of interferon-related antiviral pathways were common up to day 4 of symptoms in patients who did not require mechanical ventilator support; in those who needed mechanical ventilation, an inflammatory, activated-neutrophil and cell-stress or death (‘bacterial’) pattern was seen, even early in disease. Identifiable bacterial co-infection was not necessary for this ‘bacterial’ signature but was able to enhance its development while attenuating the early ‘viral’ signature. Our findings emphasize the importance of timing and severity in the interpretation of host responses to acute viral infection and identify specific patterns of immune-system activation that might enable the development of novel diagnostic and therapeutic tools for severe influenza.
  • Journal article
    Schwarze J, Openshaw P, Jha A, Del Giacco SR, Firinu D, Tsilochristou O, Roberts G, Selby A, Akdis C, Agache I, Custovic A, Heffler E, Pinna G, Khaitov M, Nikonova A, Papadopoulos N, Akhlaq A, Nurmatov U, Renz H, Sheikh A, Skevaki Cet al., 2018,

    Influenza burden, prevention and treatment in asthma - a scoping review by the EAACI Influenza in Asthma Task Force

    , Allergy, Vol: 73, Pages: 1151-1181, ISSN: 0105-4538

    To address uncertainties in the prevention and management of influenza in people with asthma, we performed a scoping review of the published literature on influenza burden; current vaccine recommendations; vaccination coverage; immunogenicity, efficacy, effectiveness and safety of influenza vaccines; and the benefits of antiviral drugs in people with asthma. We found significant variation in the reported rates of influenza detection in individuals with acute asthma exacerbations making it unclear to what degree influenza causes exacerbations of underlying asthma. The strongest evidence of an association was seen in studies of children. Countries in the European Union currently recommend influenza vaccination of adults with asthma; however, coverage varied between regions. Coverage was lower among children with asthma. Limited data suggest that good seroprotection and seroconversion can be achieved in both children and adults with asthma and that vaccination confers a degree of protection against influenza illness and asthma related morbidity to children with asthma. There were insufficient data to determine efficacy in adults. Overall, influenza vaccines appeared to be safe for people with asthma. We identify knowledge gaps and make recommendations on future research needs in relation to influenza in patients with asthma. This article is protected by copyright. All rights reserved.
  • Journal article
    Thwaites RS, Gunawardana NC, Broich V, Mann EH, Ahnström J, Campbell GA, Lindsley S, Singh N, Tunstall T, Lane DA, Openshaw PJ, Hawrylowicz CM, Hansel TTet al., 2018,

    Biphasic activation of complement and fibrinolysis during the human nasal allergic response

    , Journal of Allergy and Clinical Immunology, Vol: 141, Pages: 1892-1895.e6, ISSN: 0091-6749

    Complement, coagulation and fibrinolysis contribute to the pathology of many respiratory diseases. Here we detail the biphasic activation of these pathways following nasal allergen challenge. Understanding these mechanisms may lead to therapeutic insight in common respiratory diseases.
  • Journal article
    Edmondson C, Davies JC, 2018,

    Predicting the Future of Cystic Fibrosis Lung Disease: Gene Expression Holds Some of the Answers.

    , Ann Am Thorac Soc, Vol: 15, Pages: 556-557
  • Journal article
    Thwaites RS, Coates M, Ito K, Ghazaly M, Feather C, Abdulla F, Tunstall T, Jain P, Cass L, Rapeport G, Hansel TT, Nadel S, Openshaw PJet al., 2018,

    Reduced nasal viral load and IFN responses in infants with RSV bronchiolitis and respiratory failure

    , American Journal of Respiratory and Critical Care Medicine, Vol: 198, Pages: 1074-1084, ISSN: 1073-449X

    RATIONALE: Respiratory syncytial virus (RSV) bronchiolitis is a major cause of morbidity and mortality in infancy. Severe disease is thought to result from uncontrolled viral replication, an excessive immune response, or both. OBJECTIVES: To determine RSV load and immune mediator levels in nasal mucosal lining fluid by serial sampling of nasal fluids from cases of moderate and severe bronchiolitis over the course of infection. METHODS: Infants with viral bronchiolitis necessitating admission (n=55) were recruited from a paediatric centre during 2016/17. Of these, 30 were RSV infected (18 'moderate', and 12 mechanically ventilated 'severe'). Nasal fluids were sampled frequently over time using nasosorption devices and nasophayngeal aspiration (NPA). Hierarchical clustering of time weighted averages (TWA) was performed to investigate cytokine and chemokine levels, and gene expression profiling was conducted. MEASUREMENTS AND MAIN RESULTS: Unexpectedly, cases of severe RSV bronchiolitis had lower nasal viral loads and reduced interferon (IFN)-γ and CCL5/RANTES levels compared to those with moderate disease, especially when allowance was made for disease duration (all P<0.05). Reduced cytokine/chemokine levels in severe disease were also seen in children with other viral infections. Gene expression analysis of NPA samples (n=43) confirmed reduced type-I IFN gene expression in severe bronchiolitis accompanied by enhanced expression of MUC5AC and IL17A. CONCLUSIONS: Infants with severe RSV bronchiolitis have lower nasal viral load, IP-10/CXCL10 and type-I IFNs levels compared to moderately ill children, but enhanced MUC5AC and IL17A gene expression in nasal cells.
  • Journal article
    Dhariwal J, Cameron A, Wong E, Trujillo-Torralbo B, Del Rosario A, Bakhsoliani E, Paulsen M, Jackson D, Hansel TT, Edwards M, Cousins D, Walton RP, Johnston SLet al., 2018,

    Pulmonary Innate Lymphoid Cell Responses During Rhinovirus-Induced Asthma Exacerbations

    , JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 141, Pages: AB195-AB195, ISSN: 0091-6749
  • Conference paper
    Cai F, Abreu F, Ding HT, Choy D, Bremer M, Staton T, Erickson R, Peng K, Wang JS, Au-Yeung A, Hansel TT, Bjermer L, Holweg C, Yen K, Matthews JG, Scheerens Het al., 2018,

    Nasal Biomarkers Characterization In Lebrikizumab Bronchoscopy Study (CLAVIER)

    , American-Academy-of-Allergy-Asthma-and-Immunology / World-Allergy-Organization Joint Congress, Publisher: MOSBY-ELSEVIER, Pages: AB118-AB118, ISSN: 0091-6749
  • Journal article
    Thwaites RS, Jarvis HC, Singh N, Jha A, Pritchard A, Fan H, Tunstall T, Nanan J, Nadel S, Kon OM, Openshaw PJ, Hansel TTet al., 2018,

    Absorption of nasal and bronchial fluids: precision sampling of the human respiratory mucosa and laboratory processing of samples

    , Jove-Journal of Visualized Experiments, Vol: 131, ISSN: 1940-087X

    The methods of nasal absorption (NA) and bronchial absorption (BA) use synthetic absorptive matrices (SAM) to absorb the mucosal lining fluid (MLF) of the human respiratory tract. NA is a non-invasive technique which absorbs fluid from the inferior turbinate, and causes minimal discomfort. NA has yielded reproducible results with the ability to frequently repeat sampling of the upper airway. By comparison, alternative methods of sampling the respiratory mucosa, such as nasopharyngeal aspiration (NPA) and conventional swabbing, are more invasive and may result in greater data variability. Other methods have limitations, for instance, biopsies and bronchial procedures are invasive, sputum contains many dead and dying cells and requires liquefaction, exhaled breath condensate (EBC) contains water and saliva, and lavage samples are dilute and variable. BA can be performed through the working channel of a bronchoscope in clinic. Sampling is well tolerated and can be conducted at multiple sites in the airway. BA results in MLF samples being less dilute than bronchoalveolar lavage (BAL) samples. This article demonstrates the techniques of NA and BA, as well as the laboratory processing of the resulting samples, which can be tailored to the desired downstream biomarker being measured. These absorption techniques are useful alternatives to the conventional sampling techniques used in clinical respiratory research.

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